Vancomycin, linezolid, or clindamycin usually recommended for treatment of CAP or healthcare-associated pneumonia known or suspected to be caused by MRSA.19213132 For additional information regarding treatment of pneumonia, including infections caused by MRSA, consult current IDSA clinical practice guidelines available at .193132

Not indicated for treatment of respiratory tract infections caused by gram-negative bacteria.1 It is imperative that an anti-infective active against gram-negative bacteria be used concomitantly if the documented or presumptive pathogens also include gram-negative bacteria.1

Clindamycin, co-trimoxazole, a tetracycline (doxycycline or minocycline), or linezolid usually recommended for treatment of purulent cellulitis caused by MRSA; vancomycin, linezolid, daptomycin, telavancin, or clindamycin usually recommended for treatment of complicated skin and skin structure infections caused by MRSA.32 For additional information regarding treatment of skin and skin structure infections, including infections caused by MRSA, consult current IDSA clinical practice guidelines available at .222632

Not indicated for treatment of skin and skin structure infections caused by gram-negative bacteria.1 It is imperative that an anti-infective active against gram-negative bacteria be used concomitantly if the documented or presumptive pathogens also include gram-negative bacteria.1

Oral Administration

Reconstitution

Reconstitute powder for oral suspension at time of dispensing by adding amount of water specified on bottle to provide a suspension containing 100 mg/5 mL.1 After tapping bottle gently to loosen the powder, add water in 2 portions and agitate well after each addition.1

Prior to administration of each dose, gently mix suspension by inverting bottle 3–5 times; do not shake.1

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Single-use containers of linezolid injection for IV infusion should be administered without further dilution.1 Do not use the containers in series connections; do not introduce additives into the solution.13

Unless patients are carefully monitored for signs and/or symptoms of serotonin syndrome, do not use in patients with carcinoid syndrome.1

Because of risk of serotonin syndrome, generally should not be used in patients receiving SSRIs, SNRIs, tricyclic antidepressants, MAO inhibitors, or other serotonergic drugs.128 (See Specific Drugs under Interactions.)

Monitor CBCs weekly during linezolid therapy, especially in those receiving the drug for >2 weeks and in those who have preexisting myelosuppression, are receiving concomitant drugs associated with bone marrow suppression, or have a chronic infection that was or is being treated with concomitant anti-infective therapy.16

Mortality

In an investigational study in seriously ill patients with intravascular catheter-related infections†, mortality was higher in patients receiving linezolid than in patients receiving a comparator anti-infective (vancomycin, oxacillin, dicloxacillin); patients also could receive concomitant therapy for gram-negative infection.123 There was no difference in mortality between linezolid and comparator regimens in patients with only gram-positive bacteria identified in the baseline culture; mortality was higher in linezolid-treated patients with gram-negative bacterial infections, mixed gram-positive and gram-negative infections, or no pathogen identified at baseline.123 Causality not established.1

Not approved by FDA for treatment of catheter-related bacteremia or catheter-site infections; not approved for treatment of gram-negative bacterial infections.123

Monoamine Oxidase Inhibition

Linezolid is a weak, nonselective, reversible inhibitor of MAO,1234 and potentially may interact with MAO inhibitors and adrenergic and serotonergic agents.1 (See Specific Drugs under Interactions.)

Most reported cases occurred in patients receiving linezolid concomitantly with SSRIs or SNRIs.30 FDA has not concluded whether concomitant use of linezolid with other drugs with lesser degrees of serotonergic activity (e.g., tricyclic antidepressants, MAO inhibitors) is associated with a risk comparable to that reported with SSRIs or SNRIs.30

FDA states that linezolid generally should not be used in patients receiving serotonergic drugs.28 Certain life-threatening or urgent emergency situations may necessitate immediate linezolid treatment in a patient receiving a serotonergic drug, including when the anti-infective is indicated for treatment of VRE infections, nosocomial pneumonia (including cases caused by MRSA), or complicated skin and skin structure infections (including cases caused by MRSA).28 In such situations, consider availability of alternative anti-infectives and weigh benefits of linezolid against risks of serotonin syndrome.28 If linezolid is initiated, immediately discontinue the serotonergic agent.28 (See Specific Drugs under Interactions.)

Hypoglycemia

Caution patients with diabetes mellitus about potential for hypoglycemia during linezolid therapy.1 If hypoglycemia occurs, dosage reduction of insulin or oral antidiabetic agents or discontinuance of linezolid, insulin, or oral antidiabetic agents may be necessary.1

Treatment with anti-infectives can alter normal intestinal flora and may lead to overgrowth of Clostridium difficile.135

Clostridium difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all systemic anti-infectives, including linezolid, and may range in severity from mild diarrhea to fatal colitis.135C. difficile produces toxins A and B which contribute to the development of CDAD;1 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.1 Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.1

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis, angioedema, and bullous skin disorders, such as those described as Stevens-Johnson syndrome, reported.1

General Precautions

Lactic Acidosis

Lactic acidosis, characterized by recurrent nausea and vomiting, has been reported.114 Patients who develop recurrent nausea and vomiting, unexplained acidosis, or a low bicarbonate concentration while receiving linezolid should undergo immediate medical evaluation.114

Neuropathy

Peripheral and optic neuropathy, sometimes progressing to loss of vision, reported; these events have occurred principally in patients receiving the drug for >28 days.124 Blurred vision reported in some patients receiving the drug for <28 days.1

If a patient experiences symptoms of visual impairment (e.g., changes in visual acuity or color vision, blurred vision, or visual field defect), promptly perform an ophthalmic evaluation.1 Monitor visual function in all patients receiving linezolid for extended periods of time (i.e., ≥3 months).1 In addition, monitor visual function in all patients reporting a new visual symptom, regardless of length of therapy.1

Seizures

Seizures reported; history of seizures or risk factors for seizures noted in some cases.1

Selection and Use of Anti-infectives

Linezolid is indicated only for treatment of certain infections caused by certain gram-positive bacteria.1 The drug has no clinical activity against gram-negative bacteria and is not indicated for treatment of infections caused by gram-negative bacteria.1

It is imperative that an anti-infective active against gram-negative bacteria be used concomitantly if documented or presumptive pathogens also include gram-negative bacteria.1 (See Uses.)

Manufacturer states that safety and efficacy of linezolid given for >28 days have not been evaluated in controlled clinical trials.1 (See Dosage under Dosage and Administration.)

To reduce development of drug-resistant bacteria and maintain effectiveness of linezolid and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.1

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Phenylketonuria

Oral suspension contains aspartame, which is metabolized in the GI tract to provide 20 mg of phenylalanine per 5 mL of suspension.15

Other linezolid preparations do not contain aspartame;1 these other preparations should be used in individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine.1

Other Precautions

Linezolid has not been studied in patients with uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism.13 (See Contraindications under Cautions.)

Superficial tooth discoloration and tongue discoloration reported.1 In cases with known outcome, tooth discoloration was removable with professional dental cleaning (manual descaling).1

Specific Populations

Pregnancy

Lactation

Linezolid and its metabolites are distributed into milk in rats; not known whether distributed into human milk.1 Use caution.1

Pediatric Use

Safety and efficacy for treatment of vancomycin-resistant E. faecium infections, community-acquired pneumonia (CAP), nosocomial pneumonia, and complicated skin and skin structure infections in pediatric patients are supported by adequate and well-controlled studies in adults, pharmacokinetic studies in pediatric patients, and additional data from a comparator-controlled study of gram-positive infections in neonates and children through 11 years of age.1 Safety and efficacy for treatment of CAP in pediatric patients also is supported by evidence from an uncontrolled study in patients 8 months through 12 years of age.1

Safety and efficacy for treatment of uncomplicated skin and skin structure infections in pediatric patients established in a comparator-controlled study in pediatric patients 5–17 years of age.1

In children with a suboptimal response to linezolid, especially those with infections caused by pathogens with linezolid MICs of 4 mcg/mL, consider inadequate systemic exposure, site and severity of infection, and underlying medical conditions.1

Manufacturer states not recommended for empiric treatment of CNS infections in pediatric patients.1 (See Distribution under Pharmacokinetics.)

Geriatric Use

Pharmacokinetic, safety, and efficacy profiles similar to those in younger adults.12

Hepatic Impairment

Pharmacokinetics not evaluated in patients with severe hepatic impairment.1

Renal Impairment

Although clinical importance not determined, the 2 principal metabolites of linezolid may accumulate in patients with renal impairment, especially severe renal impairment.13 Weigh potential benefits against potential risks of accumulation of linezolid metabolites.1 Use with caution in severe renal impairment.5

Increased risk of serotonin syndrome, particularly with SSRIs and SNRIs;1345151617252830 unclear whether risk associated with other serotonergic drugs is comparable to that reported with SSRIs and SNRIs30

Do not use concurrently;28 if a life-threatening or urgent emergency situation necessitates immediate linezolid treatment in a patient receiving a serotonergic drug, consider availability of alternative anti-infectives and weigh benefit of linezolid against risk of serotonin syndrome28

If emergency use of linezolid is considered necessary, immediately discontinue the serotonergic drug; monitor closely for symptoms of CNS toxicity (e.g., mental changes, muscle twitching, excessive sweating, shivering/shaking, diarrhea, loss of coordination, fever) for 2 weeks (5 weeks if the patient was receiving fluoxetine) or until 24 hours after the last linezolid dose, whichever comes first28

If nonemergency use of linezolid is planned, withhold the serotonergic drug for at least 2 weeks (5 weeks if the patient was receiving fluoxetine) prior to initiating linezolid;28 serotonergic drug may be resumed 24 hours after last linezolid dose28

Do not initiate serotonergic drug in patients receiving linezolid; when necessary, initiate 24 hours after last linezolid dose28

Infants and children: Mean elimination half-life is 1.8 hours in infants >28 days through 2 months of age and 2.9 hours in children 3 months through 11 years of age.1

Adolescents 12 through 17 years of age: Mean elimination half-life is 4.1 hours.1

Special Populations

In pediatric patients, clearance varies with age and there is wide intraindividual variability.1 Excluding neonates <1 week of age, clearance is most rapid in the youngest age groups (i.e., those 7 days to 11 years of age); as children age, clearance of linezolid decreases and clearance in adolescents is similar to that observed in adults.1

Pharmacokinetics not affected by mild-to-moderate hepatic impairment (Child-Pugh class A or B).1

Pharmacokinetics of linezolid not affected by renal insufficiency, but the primary metabolites may accumulate.1 Clinical importance unclear.1

Cross-resistance between linezolid and other anti-infectives commercially available in the US is unlikely because of the drug’s unique mechanism of action.123

Advice to Patients

Advise patients that antibacterials (including linezolid) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1

Importance of completing full course of therapy, even if feeling better after a few days.1

Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with linezolid or other antibacterials in the future.1

Advise patients that linezolid may be taken orally without regard to meals.1

If using the oral suspension, importance of not shaking the bottle vigorously and gently inverting the bottle 3–5 times to resuspend the drug prior to administration of each dose.1

Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.1 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1

Importance of informing clinicians of existing or contemplated concomitant therapy including prescription drugs (e.g., antidepressants) and OTC drugs (e.g., pseudoephedrine), as well as any concomitant illnesses.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Linezolid

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For suspension

100 mg/5 mL

Zyvox

Pfizer

Tablets, film-coated

600 mg

Zyvox

Pfizer

Parenteral

Injection, for IV infusion

2 mg/mL (200 and 600 mg) in sterile isotonic solution

Zyvox Injection (in flexible containers)

Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

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